The piRNA Response to Retroviral Invasion of the Koala Genome

UMMS Affiliation

Program in Bioinformatics and Integrative Biology; Program in Molecular Medicine; Graduate School of Biomedical Sciences

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Biochemistry, Biophysics, and Structural Biology | Computational Biology | Genetic Phenomena | Genetics and Genomics | Hemic and Immune Systems | Nucleic Acids, Nucleotides, and Nucleosides


Antisense Piwi-interacting RNAs (piRNAs) guide silencing of established transposons during germline development, and sense piRNAs drive ping-pong amplification of the antisense pool, but how the germline responds to genome invasion is not understood. The KoRV-A gammaretrovirus infects the soma and germline and is sweeping through wild koalas by a combination of horizontal and vertical transfer, allowing direct analysis of retroviral invasion of the germline genome. Gammaretroviruses produce spliced Env mRNAs and unspliced transcripts encoding Gag, Pol, and the viral genome, but KoRV-A piRNAs are almost exclusively derived from unspliced genomic transcripts and are strongly sense-strand biased. Significantly, selective piRNA processing of unspliced proviral transcripts is conserved from insects to placental mammals. We speculate that bypassed splicing generates a conserved molecular pattern that directs proviral genomic transcripts to the piRNA biogenesis machinery and that this "innate" piRNA response suppresses transposition until antisense piRNAs are produced, establishing sequence-specific adaptive immunity.


AKV, KoRV-A, genome invasion, germ-line genome, koala, piRNA, piRNA clusters, retrovirus

DOI of Published Version



Cell. 2019 Oct 17;179(3):632-643.e12. doi: 10.1016/j.cell.2019.09.002. Epub 2019 Oct 10. Link to article on publisher's site

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